Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/0022-510x(71)90001-3 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
A Gain-of-Function Mutation in the Ca Channel ORAI1 Causes Stormorken Syndrome with Tubular Aggregates in Mice.
Cells
November 2024
Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Inserm U1258, CNRS UMR7104, Université de Strasbourg, 67404 Illkirch, France.
Store-operated Ca entry (SOCE) controls Ca homeostasis and mediates multiple Ca-dependent signaling pathways and cellular processes. It relies on the concerted activity of the reticular Ca sensor STIM1 and the plasma membrane Ca channel ORAI1. STIM1 and ORAI1 gain-of-function (GoF) mutations induce SOCE overactivity and excessive Ca influx, leading to tubular aggregate myopathy (TAM) and Stormorken syndrome (STRMK), two overlapping disorders characterized by muscle weakness and a variable occurrence of multi-systemic anomalies affecting spleen, skin, and platelets.
View Article and Find Full Text PDFAn Orai1 gain-of-function tubular aggregate myopathy mouse model phenocopies key features of the human disease.
EMBO J
December 2024
Department of Pharmacology and Physiology, University of Rochester Medical Center, Rochester, NY, USA.
Tubular aggregate myopathy (TAM) is a heritable myopathy primarily characterized by progressive muscle weakness, elevated levels of creatine kinase (CK), hypocalcemia, exercise intolerance, and the presence of tubular aggregates (TAs). Here, we generated a knock-in mouse model based on a human gain-of-function mutation which results in a severe, early-onset form of TAM, by inducing a glycine-to-serine point mutation in the ORAI1 pore (Orai1 or GS mice). By 8 months of age, GS mice exhibited significant muscle weakness, exercise intolerance, elevated CK levels, hypocalcemia, and robust TA presence.
View Article and Find Full Text PDFPhenotypic Heterogeneity in ORAI-1-Associated Congenital Myopathy.
Glob Med Genet
December 2024
Department of Neurology, National Institute of Mental Health and Neuro Sciences, Bengaluru, Karnataka, India.
Article Synopsis
- * The article discusses a genetically confirmed case of a young woman with progressive muscle weakness and eye movement problems, linked to a novel mutation in the ORAI-1 gene.
- * Muscle imaging revealed fatty infiltration and a biopsy indicated congenital fiber-type disproportion, expanding the known symptoms of ORAI-1-related myopathy to include these specific features.
Discovery of selective Orai channel blockers bearing an indazole or a pyrazole scaffold.
Eur J Med Chem
November 2024
Center for Drug Discovery and Translational Research, Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, 02215, USA. Electronic address:
Article Synopsis
- The calcium release activated calcium (CRAC) channel is vital in T lymphocytes for regulating immune functions, including T cell activation and cytokine production.
- Mutations in CRAC channel components can lead to severe immune disorders like SCID and muscle diseases such as tubular aggregated myopathy (TAM).
- Recent studies identified compound 4k as a promising selective blocker of the CRAC channel, effectively inhibiting T cell activity while sparing other channels like TRPM4 and TRPM7, potentially offering a new approach for therapeutic interventions.
Constitutive, Muscle-Specific Knockout Results in the Incomplete Assembly of Ca Entry Units and a Reduction in the Age-Dependent Formation of Tubular Aggregates.
Biomedicines
July 2024
Center for Advanced Studies and Technology (CAST), University G. d'Annunzio of Chieti-Pescara, I-66100 Chieti, Italy.
Article Synopsis
- - Store-operated calcium entry (SOCE) is a critical process in cells that helps them maintain calcium levels, especially when internal stores are low, and occurs in specialized regions of skeletal muscle where specific proteins are located.
- - Mutations in certain proteins associated with SOCE are linked to a muscle disorder known as tubular aggregate myopathy, which shows an increase in specific structures as muscles age, particularly in male mice.
- - A study on mice with a muscle-specific knockout of a protein called Orai1 found that these mice had a shorter lifespan, reduced weight, exercise intolerance, and more damaged mitochondria, while also showing changes in muscle structure, including a lack of tubular aggregates with age.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!